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Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis
Author(s) -
Agnello Luisa,
Colletti Tiziana,
Lo Sasso Bruna,
Vidali Matteo,
Spataro Rossella,
Gambino Caterina Maria,
Giglio Rosaria Vincenza,
Piccoli Tommaso,
Bivona Giulia,
La Bella Vincenzo,
Ciaccio Marcello
Publication year - 2021
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.14789
Subject(s) - medicine , amyotrophic lateral sclerosis , receiver operating characteristic , biomarker , gastroenterology , cerebrospinal fluid , confidence interval , area under the curve , oncology , pathology , disease , biochemistry , chemistry
Background and purpose To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. Methods We enrolled 196 ALS patients and 91 controls, who included patients with ALS‐mimicking diseases and those with non‐neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. Results Patients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver‐operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616–0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707–0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS‐R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival. Conclusions Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.